Department of physiology, Unité de Biologie et anthropologie moléculaires appliquées au développement et à la santé, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia.
Department of Cell Death and Proliferation, Instituto de Investigaciones Biomédicas de Barcelona, Consejo Superior de Investigaciones Científicas. Liver Unit Hospital Clínici Provincial, IDIBAPS and CIBERehd, 08036, Barcelona, Spain.
Biomed Pharmacother. 2018 Sep;105:573-581. doi: 10.1016/j.biopha.2018.06.017. Epub 2018 Jun 8.
Zinc has proved its efficacy in many models of ischemia reperfusion (I/R) injury. In this study, we used zinc acexamate (ZAC) as an exogenous source of zinc against renal I/R injury and we investigated whether its protective effects are mediated by the decrease of oxidative stress, inflammation, and mitochondria induced-apoptosis.
Rats were orally pretreated with vehicle or ZAC (10 or 100 mg/kg) 24 h and 30 min prior to 1 h of bilateral renal warm ischemia and 2 h of reperfusion.
Our data showed that 10 mg/kg of ZAC, but not 100 mg/kg, improved renal architecture and function. Also, the low dose of ZAC up-regulated antioxidant enzymes activities and glutathione level and decreased lipids and proteins oxidation. Interestingly, the use of ZAC resulted in a significant reduce of pro-inflammatory cytokines (IL-1ß, IL-6 and MCP-1), enhanced mitochondria integrity and decreased expression of the pro-apoptotic protein caspase-9.
We conclude that renal I/R induced oxidative stress, inflammation and apoptosis and that the use of ZAC at 10 mg/kg, but not 100 mg/kg, protects rat kidneys from I/R injury by down-regulating these processes.
锌已被证明在多种缺血再灌注（I/R）损伤模型中具有疗效。在这项研究中，我们使用锌乙酰半胱氨酸（ZAC）作为锌的外源性来源来对抗肾 I/R 损伤，并研究其保护作用是否通过降低氧化应激、炎症和线粒体诱导的细胞凋亡来介导。
大鼠在双侧肾温缺血前 1 小时和再灌注前 24 小时和 30 分钟用载体或 ZAC（10 或 100mg/kg）口服预处理。
我们的数据表明，10mg/kg 的 ZAC，但不是 100mg/kg，改善了肾脏结构和功能。此外，低剂量的 ZAC 上调了抗氧化酶的活性和谷胱甘肽水平，并降低了脂质和蛋白质的氧化。有趣的是，使用 ZAC 导致促炎细胞因子（IL-1β、IL-6 和 MCP-1）显著减少，线粒体完整性增强，促凋亡蛋白 caspase-9 的表达减少。
我们得出结论，肾 I/R 诱导氧化应激、炎症和细胞凋亡，而使用 10mg/kg 的 ZAC，但不是 100mg/kg，可以通过下调这些过程来保护大鼠肾脏免受 I/R 损伤。
